Continuous normobaric hypoxia (CNH) renders the heart more tolerant to acute ischemia/reperfusion injury. Protein kinase C (PKC) is an important component of the protective signaling pathway, but the contribution of individual PKC isoforms under different hypoxic conditions is poorly understood. The aim of this study was to analyze the expression of PKCepsilon after the adaptation to CNH and to clarify its role in increased cardiac ischemic tolerance with the use of PKCepsilon inhibitory peptide KP-1633. Adult male Wistar rats were exposed to CNH (10 % O(2), 3 weeks) or kept under normoxic conditions. The protein level of PKCepsilon and its phosphorylated form was analyzed by Western blot in homogenate, cytosolic and particulate fractions; the expression of PKCepsilon mRNA was measured by RT-PCR. The effect of KP-1633 on cell viability and lactate dehydrogenase (LDH) release was analyzed after 25-min metabolic inhibition followed by 30-min re-energization in freshly isolated left ventricular myocytes. Adaptation to CNH increased myocardial PKCepsilon at protein and mRNA levels. The application of KP-1633 blunted the hypoxia-induced salutary effects on cell viability and LDH release, while control peptide KP-1723 had no effect. This study indicates that PKCepsilon is involved in the cardioprotective mechanism induced by CNH.
- MeSH
- fyziologická adaptace genetika MeSH
- hypoxie enzymologie genetika patofyziologie MeSH
- inhibitory proteinkinas farmakologie MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- messenger RNA biosyntéza genetika MeSH
- potkani Wistar MeSH
- proteinkinasa C-epsilon antagonisté a inhibitory biosyntéza genetika MeSH
- reperfuzní poškození myokardu enzymologie genetika MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory proteinkinas MeSH
- L-laktátdehydrogenasa MeSH
- messenger RNA MeSH
- Prkce protein, rat MeSH Prohlížeč
- proteinkinasa C-epsilon MeSH
Increasing hemodynamic load during early postnatal development leads to rapid growth of the left ventricular (LV) myocardium, which is associated with membrane phospholipid (PL) remodeling characterized by n-3 polyunsaturated fatty acids (PUFA) accumulation. The aim of this study was to examine the influence of additional workload imposed early after birth when ventricular myocytes are still able to proliferate. Male Wistar rats were subjected to abdominal aortic constriction (AC) at postnatal day 2. Concentrations of PL and their fatty acid (FA) profiles in the LV were analyzed in AC, sham-operated (SO) and intact animals on postnatal days 2 (intact only), 5 and 10. AC resulted in LV enlargement by 22 % and 67 % at days 5 and 10, respectively, compared with age-matched SO littermates. Concentrations of phosphatidylcholine, cardiolipin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine and sphingomyelin decreased in AC myocardium, albeit with different time course and extent. The main effect of AC on FA remodeling consisted in the accumulation of n-3 PUFA in PL. The most striking effect of AC on FA composition was observed in phosphatidylinositol and cardiolipin. We conclude that excess workload imposed by AC inhibited the normal postnatal increase of PL concentration while further potentiating the accumulation of n-3 PUFA as an adaptive response of the developing myocardium to accelerated growth.
- MeSH
- aorta abdominalis MeSH
- fosfolipidy metabolismus MeSH
- hemodynamika MeSH
- krevní tlak MeSH
- krysa rodu Rattus MeSH
- kyseliny mastné omega-3 metabolismus MeSH
- myokard cytologie metabolismus MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- proliferace buněk MeSH
- stenóza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fosfolipidy MeSH
- kyseliny mastné omega-3 MeSH
PURPOSE: To assess the impact of clinical and nutritional factors on overall survival (OS) and time to disease progression of oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: We retrospectively studied and analysed several clinical and nutritional factors, such as performance status, weight changes before and during CRT, dysphagia, nutritional support, and serum albumin to see whether they exerted any impact on OS and time to disease progression. RESULTS: In 107 patients the average weight loss was 9.7% from the onset of signs of disease to the beginning of therapy and 3% during CRT. In univariate analysis, significant unfavorable impact on survival was proved for low performance status, severe dysphagia, need for nasogastric tube insertion, above-average weight loss before treatment, weight loss >5% during CRT, and serum albumin ≤ 35 g/l before or after CRT. Patients supported by oral nutritional supplements (ONS) had higher probability to attain full dosage of CRT and radical resection than did those obtaining dietary advice alone. In multivariate analysis, serum albumin level, nasogastric (NG) tube insertion and pretreatment body weight loss were independent prognostic factors for OS, while serum albumin level after CRT and NG tube insertion were prognosticators for time to progression. CONCLUSION: Serum albumin level can serve as a useful prognostic factor for the outcome of patients with oesophageal cancer treated with neoadjuvant CRT and surgery. Appropriate nutritional support of these patients increased the probability of attaining full dosage of CRT and radical disease resection.
- MeSH
- časové faktory MeSH
- celková dávka radioterapie MeSH
- dospělí MeSH
- ezofagektomie * MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory jícnu mortalita terapie MeSH
- následné studie MeSH
- neoadjuvantní terapie MeSH
- nutriční stav * MeSH
- poruchy polykání * MeSH
- předoperační péče MeSH
- prognóza MeSH
- progrese nemoci MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chronic intermittent hypoxia (CIH) is associated with increased production of reactive oxygen species that contributes to the adaptive mechanism underlying the improved myocardial ischemic tolerance. The aim was to find out whether the antioxidative enzyme manganese superoxide dismutase (MnSOD) can play a role in CIH-induced cardioprotection. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 25 exposures) (n=14) or kept at normoxia (n=14). Half of the animals from each group received N-acetylcysteine (NAC, 100 mg/kg) daily before the hypoxic exposure. The activity and expression of MnSOD were increased by 66 % and 23 %, respectively, in the mitochondrial fraction of CIH hearts as compared with the normoxic group; these effects were suppressed by NAC treatment. The negative correlation between MnSOD activity and myocardial infarct size suggests that MnSOD can contribute to the improved ischemic tolerance of CIH hearts.
- MeSH
- acetylcystein farmakologie terapeutické užití MeSH
- hypoxie * MeSH
- krysa rodu Rattus MeSH
- mitochondrie metabolismus MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- reperfuzní poškození myokardu metabolismus prevence a kontrola MeSH
- scavengery volných radikálů farmakologie terapeutické užití MeSH
- superoxiddismutasa genetika metabolismus MeSH
- upregulace * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcystein MeSH
- reaktivní formy kyslíku MeSH
- scavengery volných radikálů MeSH
- superoxiddismutasa MeSH
Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms alpha, delta and epsilon in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of (32)P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (10(5) g) and nuclear-cytoskeletal-myofilament-enriched (10(3) g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the third day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCdelta, which increased significantly at d10 in the cytosolic fraction at the expense of the membrane-enriched fraction. It is concluded that PKCalpha, PKCdelta and PKCepsilon undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period.
- MeSH
- časové faktory MeSH
- fosforylace MeSH
- frakcionace buněk MeSH
- histony metabolismus MeSH
- hypertenze komplikace enzymologie patologie patofyziologie MeSH
- izoenzymy MeSH
- krevní tlak MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- myokard enzymologie patologie MeSH
- nemoci srdce enzymologie etiologie patologie patofyziologie MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- proteinkinasa C-alfa metabolismus MeSH
- proteinkinasa C-delta metabolismus MeSH
- proteinkinasa C-epsilon metabolismus MeSH
- proteinkinasa C metabolismus MeSH
- upregulace MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- histony MeSH
- izoenzymy MeSH
- Prkcd protein, rat MeSH Prohlížeč
- Prkce protein, rat MeSH Prohlížeč
- proteinkinasa C-alfa MeSH
- proteinkinasa C-delta MeSH
- proteinkinasa C-epsilon MeSH
- proteinkinasa C MeSH
Fluorophore types and their photochemical stability have been tested in two samples of humic acids (HA) and four types of fulvic acids (FA) extracted from upper soil horizons (O and A horizons) in Norway spruce forest mountain ecosystems. Only one type of fluorophore occurred in all samples, with an excitation maximum at 310 nm for both HA and FA samples and emission maxima between 420-435 and 440-450 for HA and FA, respectively. HA weak native fluorescence increased significantly during irradiation in the first 12 h. Fluorophores in FA were uniformly degraded from the beginning of irradiation. Addition of metal (aluminium or ferric) ions did not affect the positions of fluorescence maxima in any of the studied samples; mild effects on fluorescence intensities were observed.
- MeSH
- benzopyrany chemie MeSH
- fluorescenční barviva chemie MeSH
- hliník chemie MeSH
- huminové látky analýza MeSH
- ionty MeSH
- ultrafialové záření * MeSH
- železo chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzopyrany MeSH
- fluorescenční barviva MeSH
- fulvic acid MeSH Prohlížeč
- hliník MeSH
- huminové látky MeSH
- ionty MeSH
- železo MeSH
Normal increase in hemodynamic load during early postnatal life is associated with heart growth and maturation of membrane structures that is accompanied by remodeling of membrane protein and lipid components. This review describes remodeling of phospholipids (PL) in rat myocardium during normal postnatal development and during accelerated cardiac growth induced by additional workload (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart early after birth. Normal physiological load after birth stimulates the development of membrane structures and synthesis of PL. While hyperthyroidism accelerates these processes, pressure overload has an inhibitory effect. These changes primarily influence the maturation of mitochondrial membranes as cardiolipin is one of the most affected PL species. The most sensitive part of PL structure in their remodeling process are PL acyl chains, particularly polyunsaturated fatty acids that are the key components determining the basic physicochemical properties of the membrane bilayer and thus the function of membrane-bound proteins and membrane-derived signaling lipid molecules. It is evident that PL remodeling may significantly influence both normal and pathological postnatal development of myocardium.
- MeSH
- fosfolipidy chemie metabolismus MeSH
- fyziologická adaptace MeSH
- hemodynamika * MeSH
- krysa rodu Rattus MeSH
- mitochondriální membrány metabolismus MeSH
- molekulární konformace MeSH
- myokard metabolismus MeSH
- nemoci srdce metabolismus patofyziologie MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- srdce růst a vývoj patofyziologie MeSH
- srdeční mitochondrie metabolismus MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- fosfolipidy MeSH
- nenasycené mastné kyseliny MeSH
BACKGROUND: Oesophageal cancer patients with substantial weight loss have worse prognosis. Weight loss is often refractory to the nutritional support. Causes of the weight loss are multiple: oesophageal stricture, frequent alcohol abuse, cancer related cachexia. It may be a consequence of metabolic changes mediated by cytokines, hormones and tumour derived products. Leptin, a protein produced by adipocytes, is an important signalling molecule in energy regulation, metabolism of fatty acids and it can also augment tumour growth of various cancer cell lines. Enhanced intake of poly-unsaturated fatty acids may play an important role in the reversal of cancer related weight loss. METHODS AND RESULTS: In this study we examined the nutritional status (pre-treatment weight-loss, actual weight, body mass index), serum levels of leptin, soluble leptin receptor, TNF-alpha, IGF-1 and plasma phosphatidyl-cholin fatty acids before the beginning of treatment, after the onset of treatment and shortly before its completion. In the group of 38 pts (33 men, 5 women), mean age 58 years, statistically significant mean pre-treatment weight-loss 8 kg and significant mean weight loss 2 kg after chemoradiotherapy was observed. Concomitant chemoradiation led to transient elevation of serum leptin level despite the weight loss during chemoradiotherapy. Significant changes in the distribution of fatty acids in plasmatic phosphatidyl-cholin were observed. CONCLUSIONS: Our results show the possibility for direct influence of chemoradiotherapy on body weight regulation in advanced oesophageal cancer patients.
- MeSH
- dospělí MeSH
- fosfatidylcholiny chemie MeSH
- hmotnostní úbytek MeSH
- insulinu podobný růstový faktor I analýza MeSH
- kombinovaná terapie MeSH
- leptin krev MeSH
- leptinové receptory MeSH
- lidé středního věku MeSH
- lidé MeSH
- mastné kyseliny krev MeSH
- nádory jícnu krev terapie MeSH
- receptory buněčného povrchu krev MeSH
- senioři MeSH
- TNF-alfa analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylcholiny MeSH
- insulinu podobný růstový faktor I MeSH
- LEPR protein, human MeSH Prohlížeč
- leptin MeSH
- leptinové receptory MeSH
- mastné kyseliny MeSH
- receptory buněčného povrchu MeSH
- TNF-alfa MeSH
Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. The pattern of plasma fatty acids influences the levels of plasma lipids and lipoproteins. The concentration of plasma lathosterol is a surrogate marker of cholesterol synthesis de novo, concentrations of campesterol and beta-sitosterol reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationship to plasma lipids, lipoproteins, cholesterol precursors and plant sterols. We examined 16 women with anorexia nervosa and 25 healthy ones. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol. Moreover, a decreased content of n-6 polyunsaturated fatty acids was found in all lipid classes. These changes were compensated by an increased content of monounsaturated fatty acids in cholesteryl esters, saturated fatty acids in triglycerides and both monounsaturated and saturated fatty acids in phosphatidylcholine. The most consistent finding in the fatty acid pattern concerned a decreased content of linoleic acid and a raised content of palmitoleic acid in all lipid classes. The changes of plasma lipids and lipoproteins in anorexia nervosa are the result of complex mechanisms including decreased catabolism of triglyceride-rich lipoproteins, normal rate of cholesterol synthesis and increased resorption of exogenous cholesterol.
- MeSH
- apolipoproteiny krev MeSH
- chromatografie plynová MeSH
- dospělí MeSH
- estery cholesterolu krev MeSH
- fosfatidylcholiny krev MeSH
- jaterní testy MeSH
- lidé MeSH
- lipidy krev MeSH
- lipoproteiny krev MeSH
- mastné kyseliny krev MeSH
- mentální anorexie krev MeSH
- steroly krev MeSH
- triglyceridy krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- apolipoproteiny MeSH
- estery cholesterolu MeSH
- fosfatidylcholiny MeSH
- lipidy MeSH
- lipoproteiny MeSH
- mastné kyseliny MeSH
- steroly MeSH
- triglyceridy MeSH
